Type I allergy is an inflammatory response which is elicited as the invasion of exogenous agents into the body triggers the release of various enzymes and chemical mediators, such as histamine and leukotrienes, from mast cells and eosinophils, which in turn induce tissue-damaging inflammations. The allergic response, when generalized, can lead to a systemic and often life threatening reaction known as anaphylactic shock.
The agents which trigger an anaphylactic shock response include various drugs, such as penicillin and insulin, sources of desensitizing allergens such as ticks and fungi, dietary allergens such as eggs and peanuts, iodine-containing contrast media, local anesthetics and so on.
The current pharmacotherapy for anaphylactic shock consists of the administration of epinephrine and steroids. It is reported that if early therapy is judiciously instituted, the prognosis for this condition is generally satisfactory. However, these current treatments are no more than symptomatic remedies and the prophylaxis of anaphylactic shock is considered to be truly important. However, there is no established prophylactic modality for anaphylactic shock, and the current clinical practice appears to be based, at best, on the vague concept of preventing the invasion of high-risk foreign agents.
Therefore, in patients requiring certain drugs, such as penicillin and other antibiotics, and in cases in which an iodine contrast medium is used in X-ray diagnosis, these agents are administered of necessity, despite the attendant risk of anaphylactic shock. Thus, there is a pressing need for a positive prophylactic measure against such vigorous immune system responses.
In pollen allergy, symptoms occur preferentially in the nose and eye. Recent years have witnessed a rapid increase in the number of patients who complain of the so-called pollinosis syndrome due to pollens of cedar and other allergenic plants, resulting in, for example, allergic conjuctivitis and allergic rhinitis (eye watering, sinus congestion, nasal congestion, sneezing and the like).
For the prevention of pollen disease, a prophylactic treatment with antiallergic agents, a symptomatic treatment with antihistamines and steroids, and hyposensitization therapy are generally indicated at present.
However, there is not available as yet an antiallergic agent effective enough as a preventive drug, and the antihistamines and steroids in current use for symptomatic treatment have the problem of side effects.
Atopy provides hereditary basis for allergic responses. The condition is revealed as a congenital hypersensitivity to specific agents and is usually manifested as bronchial asthma and allergic rhinitis in the patient and his family.
Atopic dermatitis is an inflammatory disease of the skin, which may arise because of a predisposition and which is often characterized by areas of localized itch. It is also known that as the affected area is scratched, the local eruption can be aggravated so that the disease runs a chronic course. Moreover, the pruritus associated with atopic dermatitis develops suddenly in many cases and tends to be provoked and intensified by the slightest stimulation.
A variety of treatments have been attempted for atopic dermatitis, but they have proved unsuccessful. The current therapeutic modality for this disease consists of the topical treatment primarily with topical adrenocorticoids and, as an adjunct therapy, antipruritic agents such as antihistamines. But since these drugs are not free from side effects, the advent of a safe and more sure-acting drug for the prevention and treatment of atopic dermatitis has been awaited in earnest.
Patients with bronchial asthma are rapidly increasing in number and present a serious problem everywhere in the world today. Bronchial asthma is an airway disease, the cardinal manifestation of which is respiratory distress due to paroxysmal airway constriction, which is life-threatening at times.
While many etiologic agents are usually involved in the onset of bronchial asthma, the chief cause is generally believed to be an increased airway responsiveness due to allergic factors associated with inhaled antigens such as ticks, pollen, dust and so on.
For the treatment of bronchial asthma, prophylaxis with antiallergic drugs and symptomatic treatment with .beta.-receptor stimulants and steroids is practiced today, but there is no antiallergic drug effective enough as a prophylactic. Further, the problem of side effects has been pointed out frequently with the use of .beta.-receptor stimulants and steroids used for symptomatic treatment.
A high affinity immunoglobulin E receptor (Fc.epsilon.RI) is a glycoprotein having a tetrameric structure consisting of an .alpha.-chain, a .beta.-chain and two disulfidized .gamma.-chains. It has been reported that a soluble fragment of Fc.epsilon.RI .alpha.-chain (sFc.epsilon.RI.alpha.) is produced by a genetic engineering techniques using DHFR-deficient CHO cells and that only the extracellular region of the .alpha.-chain is involved in the high-affinity binding to IgE [Blank, U. et al., J. Biol. Chem., 266, 2639 (1991)].